Molecular Express specializes in the design and engineering of functionalized liposomes for drug delivery and vaccine development. In previous studies, an extensive set of liposome formulations were screened to establish the optimal lipid combination that meets certain physicochemical parameters and provides strong immune responses in animals. These unilamellar vesicles have diameters of approximately 100 nm, are stable (i.e., no aggregation, precipitation or degradation of the components for over a year) in biological buffer solutions, and are commercially scalable. The immunogenic liposome compositions form the basis of a vaccine platform technology called the VesiVax(r) system. The VesiVax(r) system was designed to be easily manipulated, so that target antigens could be displayed from the surface of the immunogenic liposomes for subsequent use in immunization studies. Vaccines based on the VesiVax(r) system can be engineered using two formats: i) target antigens or adjuvant proteins can be engineered to be expressed as a fusion protein with a hydrophobic domain (HD), which facilitates its incorporation into the liposomes or; ii) target antigens or adjuvants in the form of proteins, peptides or carbohydrates can be attached via conjugation to the surface of the liposomes (i.e., conjugatable adjuvant lipid vesicles; CALVs). The flexibility of the VesiVax(r) platform allows both antigens and adjuvants to be formulated together into the liposomes thus maximizing the immune response. In this SBIR AT Phase I proposal, we intend to establish the utility of the VesiVax(r) CALV platform as an effective adjuvant for virus-like particles (VLPs). To demonstrate this concept, we propose to prepare VesiVax(r) CALV formulations containing different Toll-like Receptor (TLR) agonists and then conjugating them to VLPs that have been designed to express HIV antigens (HIV-VLPs) (Specific Aim 1). The VesiVax(r) CALV HIV-VLPs will then be tested in mouse and rabbit models (Specific Aim 2). These studies are potentially of high impact because demonstration that: I) the VesiVax(r) CALVs can adjuvant VLPs would have an immediate impact through increasing sales of the CALV line of research kits; II) the sublingual route of administration stimulates potent immune responses would be another useful application of the VesiVax(r) technology and; III) one or more VesiVax(r) CALV HIV-VLP formulations stimulate potent HIV antibody neutralization activity in the in vitro assays will set the stage for the selection of one or more of these candidates to undergo further testing in non-human primates prior to final selection of a VesiVax(r) CALV HIV-VLP candidate that will be advanced to clinical testing. Such a vaccine will provide the basis for a cost effective HIV immunization strategy that could be implemented on a global scale.